Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

Liat Samuelov; Ofer Sarig; Robert M. Harmon; Debora Rapaport; Akemi Ishida-Yamamoto; Ofer Isakov; Jennifer L. Koetsier; Andrea Gat; Ilan Goldberg; Reuven Bergman; Ronen Spiegel; Ori Eytan; Shamir Geller; Sarit Peleg; Noam Shomron; Christabelle S. M. Goh; Neil J. Wilson; Frances J. D. Smith; Elizabeth Pohler; Michael A. Simpson; W. H. Irwin McLean; Alan D. Irvine; Mia Horowitz; John A. McGrath; Kathleen J. Green; Eli Sprecher

doi:10.1038/ng.2739

Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

Liat Samuelov
, Ofer Sarig
, Robert M. Harmon
, Debora Rapaport
, Akemi Ishida-Yamamoto
, Ofer Isakov
, Jennifer L. Koetsier
, Andrea Gat
, Ilan Goldberg
, Reuven Bergman
, Ronen Spiegel
, Ori Eytan
, Shamir Geller
, Sarit Peleg
, Noam Shomron
, Christabelle S. M. Goh
, Neil J. Wilson
, Frances J. D. Smith
, Elizabeth Pohler
, Michael A. Simpson

W. H. Irwin McLean, Alan D. Irvine, Mia Horowitz, John A. McGrath, Kathleen J. Green, Eli Sprecher

Research output: Contribution to journal › Letter › peer-review

289 Citations (Scopus)

Abstract

The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and have a crucial role in maintaining epidermal integrity and barrier function. Mutations causing SAM syndrome resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. Our deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.

Original language	English
Journal	Nature Genetics
Early online date	25 Aug 2013
DOIs	https://doi.org/10.1038/ng.2739
Publication status	Published - 2013

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10.1038/ng.2739

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Samuelov, L., Sarig, O., Harmon, R. M., Rapaport, D., Ishida-Yamamoto, A., Isakov, O., Koetsier, J. L., Gat, A., Goldberg, I., Bergman, R., Spiegel, R., Eytan, O., Geller, S., Peleg, S., Shomron, N., Goh, C. S. M., Wilson, N. J., Smith, F. J. D., Pohler, E., ... Sprecher, E. (2013). Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nature Genetics. https://doi.org/10.1038/ng.2739

@article{652f82c13a4f4e0fb4291bb4f27ad497,

title = "Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting",

abstract = "The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and have a crucial role in maintaining epidermal integrity and barrier function. Mutations causing SAM syndrome resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. Our deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.",

author = "Liat Samuelov and Ofer Sarig and Harmon, \{Robert M.\} and Debora Rapaport and Akemi Ishida-Yamamoto and Ofer Isakov and Koetsier, \{Jennifer L.\} and Andrea Gat and Ilan Goldberg and Reuven Bergman and Ronen Spiegel and Ori Eytan and Shamir Geller and Sarit Peleg and Noam Shomron and Goh, \{Christabelle S. M.\} and Wilson, \{Neil J.\} and Smith, \{Frances J. D.\} and Elizabeth Pohler and Simpson, \{Michael A.\} and McLean, \{W. H. Irwin\} and Irvine, \{Alan D.\} and Mia Horowitz and McGrath, \{John A.\} and Green, \{Kathleen J.\} and Eli Sprecher",

year = "2013",

doi = "10.1038/ng.2739",

language = "English",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

}

Samuelov, L, Sarig, O, Harmon, RM, Rapaport, D, Ishida-Yamamoto, A, Isakov, O, Koetsier, JL, Gat, A, Goldberg, I, Bergman, R, Spiegel, R, Eytan, O, Geller, S, Peleg, S, Shomron, N, Goh, CSM, Wilson, NJ, Smith, FJD, Pohler, E, Simpson, MA, McLean, WHI, Irvine, AD, Horowitz, M, McGrath, JA, Green, KJ & Sprecher, E 2013, 'Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting', Nature Genetics. https://doi.org/10.1038/ng.2739

TY - JOUR

T1 - Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

AU - Samuelov, Liat

AU - Sarig, Ofer

AU - Harmon, Robert M.

AU - Rapaport, Debora

AU - Ishida-Yamamoto, Akemi

AU - Isakov, Ofer

AU - Koetsier, Jennifer L.

AU - Gat, Andrea

AU - Goldberg, Ilan

AU - Bergman, Reuven

AU - Spiegel, Ronen

AU - Eytan, Ori

AU - Geller, Shamir

AU - Peleg, Sarit

AU - Shomron, Noam

AU - Goh, Christabelle S. M.

AU - Wilson, Neil J.

AU - Smith, Frances J. D.

AU - Pohler, Elizabeth

AU - Simpson, Michael A.

AU - McLean, W. H. Irwin

AU - Irvine, Alan D.

AU - Horowitz, Mia

AU - McGrath, John A.

AU - Green, Kathleen J.

AU - Sprecher, Eli

PY - 2013

Y1 - 2013

N2 - The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and have a crucial role in maintaining epidermal integrity and barrier function. Mutations causing SAM syndrome resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. Our deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.

AB - The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and have a crucial role in maintaining epidermal integrity and barrier function. Mutations causing SAM syndrome resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. Our deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.

UR - https://www.scopus.com/pages/publications/84885019283

U2 - 10.1038/ng.2739

DO - 10.1038/ng.2739

M3 - Letter

C2 - 23974871

SN - 1061-4036

JO - Nature Genetics

JF - Nature Genetics

ER -

Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

Abstract

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Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)

Human and Mouse Genetics Studies of Filaggrin-Related Proteins in Eczema and Allergy (Joint with Trinity College Dublin)

Aref#d: 22163. The Establishment of a Large Case Collection of Childhood Atopic Dermatitis: A Resource for Gemetoc Research (Joint with Trinity College Dublin)

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Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

Abstract

Access to Document

Other files and links

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Projects

Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)

Human and Mouse Genetics Studies of Filaggrin-Related Proteins in Eczema and Allergy (Joint with Trinity College Dublin)

Aref#d: 22163. The Establishment of a Large Case Collection of Childhood Atopic Dermatitis: A Resource for Gemetoc Research (Joint with Trinity College Dublin)

Cite this